MAP3K8 p.Glu370=
c.1110G>A · rs763097220 · VCV1528993
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.1 | GERP -0.34, phastCons 1 |
| Overall | ||
| CADD | 8.583 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,074 alleles
Filtering AF
0.00844%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00661%
Overall
0.000991%
16/1,614,040 alleles · ultra-rare
exomes 15/1,461,882 · genomes 1/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,074 |
| South Asian | 0.0143% | 7,007 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| African / African-American | 0.00133% | 74,908 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- MAP3K8
- Protein
- p.Glu370=
- Coding
- c.1110G>A
- MANE Select
- NM_005204
- dbSNP
- rs763097220
- Type
- single nucleotide variant
- Location
- chr10:30459338 (GRCh38)
- Gene constraint
- LOEUF 0.58 · pLI 0.73 (gnomAD)
- Structure
- AlphaFold pLDDT 74.13 · 3 PDB
- Residue 370
- the protein kinase domain
Similar variants
- MAP3K8 p.Glu370Lys Uncertain significance ★ ⚠ same residue
- MAP3K8 p.Ala35Ser Uncertain significance ★★ ⚠ same type
- MAP3K8 p.Ala450Thr Uncertain significance ★★ same type
- MAP3K8 p.Arg392Gly Uncertain significance ★★ ⚠ same type
- MAP3K8 p.Arg408Ser Uncertain significance ★★ ⚠ same type
- MAP3K8 p.Asn54Asp Uncertain significance ★★ ⚠ same type
- MAP3K8 p.Gly67Asp Uncertain significance ★★ ⚠ same type
- MAP3K8 p.Ile190Val Uncertain significance ★★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/map3k8-p-glu370 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown